Details

Autor(en) / Beteiligte

• Duhan, Vikas
• Hamdan, Thamer A
• Xu, Haifeng C
• Shinde, Prashant
• Bhat, Hilal
• Li, Fanghui
• Al-Matary, Yahya
• Häussinger, Dieter
• Bezgovsek, Judith
• Friedrich, Sarah-Kim
• Hardt, Cornelia
• Lang, Philipp A
• Lang, Karl S
• Selin, Liisa

Titel

NK cell-intrinsic FcεRIγ limits CD8+ T-cell expansion and thereby turns an acute into a chronic viral infection

Ist Teil von

• PLoS pathogens, 2019-06, Vol.15 (6), p.e1007797-e1007797

Ort / Verlag

United States: Public Library of Science

Erscheinungsjahr

2019

Quelle

MEDLINE

Beschreibungen/Notizen

• During viral infection, tight regulation of CD8+ T-cell functions determines the outcome of the disease. Recently, others and we determined that the natural killer (NK) cells kill hyperproliferative CD8+ T cells in the context of viral infection, but molecules that are involved in shaping the regulatory capability of NK cells remain virtually unknown. Here we used mice lacking the Fc-receptor common gamma chain (FcRγ, FcεRIγ, Fcer1g-/- mice) to determine the role of Fc-receptor and NK-receptor signaling in the process of CD8+ T-cell regulation. We found that the lack of FcRγ on NK cells limits their ability to restrain virus-specific CD8+ T cells and that the lack of FcRγ in Fcer1g-/- mice leads to enhanced CD8+ T-cell responses and rapid control of the chronic docile strain of the lymphocytic choriomeningitis virus (LCMV). Mechanistically, FcRγ stabilized the expression of NKp46 but not that of other killer cell-activating receptors on NK cells. Although FcRγ did not influence the development or activation of NK cell during LCMV infection, it specifically limited their ability to modulate CD8+ T-cell functions. In conclusion, we determined that FcRγ plays an important role in regulating CD8+ T-cell functions during chronic LCMV infection.